Neurocognitive and emotional factors predict pain-related healthcare utilization in children with sickle cell disease.

DMD is an X-linked genetic multifactorial condition in which the lack of the protein dystrophin causes progressive muscular weakness, cardiomyopathy and respiratory insufficiency. DMD is caused by mutations in the dystrophin gene, which is the largest gene in the human genome and it is composed of 79 exons; its expression is regulated by different promoters with distinct tissue specificity. It contains 3 promoter regions encoding full-length isoforms (Dp427) and at least 4 internal promoter regions encoding the shorter isoforms (Dp260, Dp140, Dp116 and Dp71/Dp40). Outside of the muscular tissue, full length Dp427 isoforms are primarily expressed in the cortical/cerebral structures (Dp427c) and in the cerebellar Purkinje cells (Dp427p). By contrast, shorter isoforms are transcribed in the central nervous system (CNS) but not in muscle []. More precisely, the Dp260 is mainly expressed in the retina, the Dp140 and Dp71 are widely expressed in the CNS, the Dp116 is expressed in the peripheral-nerve Schwann cells and the Dp40 has been detected in central neuronal synapses [–]. DMD individuals typically present with intragenic loss of function mutations of the dystrophin [, ]. Several studies identified a greater vulnerability to brain comorbidities in DMD patients with mutations in the 3’ end of the dystrophin gene, affecting specifically the Dp140 and Dp71 isoforms [–].